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Objective: Nonuniformity in suppression of spermatogenesis induced by various hormones or hormone combinations has impeded the development of an effective hormonal male contraceptive. The basis for this heterogeneity in response remained unresolved to date; however, the presence of ethnic differences points to an involvement of genetic factors., Patients and Measurements: In a retrospective analysis we investigated the impact of a CAG repeat polymorphism in the androgen receptor and polymorphic sites in the oestrogen and FSH receptor genes on spermatogenic suppression in 85 Caucasian men treated with different regimens of hormonal contraception., Results: Failure to reduce sperm concentrations below 3 million/ml was significantly associated with insufficient suppression of gonadotrophins. The extent of gonadotrophin suppression was not explained by any polymorphism but was primarily pharmacological, resulting from addition of gestagens to testosterone. When LH and FSH suppression was rapid and persistent none of the polymorphisms studied explained why some men failed to achieve azoospermia. In cases with incomplete gonadotrophin suppression the chances of becoming azoospermic were 2.5 times higher in men having more than 22 CAG repeats., Conclusions: In summary, our analysis shows that in a subset of men, effective hormonal male contraception can be achieved even in the absence of complete gonadotrophin suppression.

Follicle stimulating hormone (FSH) plays a key role in the maintenance of qualitatively and quantitatively normal spermatogenesis. It controls gamete development through Sertoli cells, via binding to its receptor. The influence and importance of FSH receptor (FSHR) variants on Sertoli cell function is not completely understood and remains to be investigated. In this retrospective study, we explored the impact and action of two distinct FSHR isoforms, Thr307/Asn680 and Ala307/Ser680, in a large group of men. This investigation includes 288 normal healthy men, 86 of whom were proven fathers previously studied, and 202 were newly recruited subjects. The FSHR polymorphism at position 680 was analyzed in the whole group, while position 307 was investigated in 150 subjects, both of them by single-stranded conformation polymorphism (SSCP) gel electrophoresis. The distribution frequency for position 680 was 29% for the Asn/Asn, 52% for the Asn-Ser, 19% for the Ser-Ser variant, and for position 307, 27% for the Thr-Thr, 55% for the Ala-Thr, 18% for the Ala-Ala, respectively. Polymorphism combinations that were different from Thr307/Asn680 - Ala307/Ser680 were found in four subjects. When subjects were grouped according to genotype at position 680, no significant differences between basal FSH, testosterone, inhibin B levels and semen parameters were found. This clinical finding demonstrates that, differently from females, in whom a significant correlation between FSHR polymorphism and basal FSH levels was found, the FSHR genotype has no influence on clinical parameters in males.